Alzheimer disease (AD) is the most common cause of dementia and is an increasing public health problem. Genetic, biochemical, and animal model studies suggest the accumulation and conformational change of amyloid-beta (A[unreadable]) is a major contributor to the pathogenesis of AD. We propose to determine if A[unreadable] production and clearance rates are altered in sporadic Alzheimer Disease versus controls. We will determine if the major genetic risk factor for AD is associated with decreased A[unreadable] clearance. We will measure A[unreadable] dynamic variations and correlate with any changes in A[unreadable] clearance or production rates. Overall, this study will provide the first measurements of A[unreadable] production and clearance in Alzheimer's disease and measure the effect of the major genetic risk factor in humans (APOE). This information will likely provide insights into the pathogenesis of AD by determining the contribution of overproduction or decreased clearance of A[unreadable]. Eventually, this may lead to improved diagnostic or predictive testing for AD as well as aid in the evaluation of new disease modifying therapeutics.